CARRIER AND PRENATAL DIAGNOSIS OF MENKES DISEASE
Gu YH1,2 , Kodama H1,
Murata Y1, Ushijima H2
1 Dept. of Pediatrics,
Teikyo University School of Medicine, Tokyo, Japan
2 Dept. of Developmental
Medical Sciences, School of International Health, Graduate School of
Medicine, The University of Tokyo, Tokyo, Japan
Objective: Menkes disease (MND) is
an X-linked recessive neurodegenerative disorder caused by defects in ATP7A
gene. To MND early diagnosis are very important because initiating
treatment over 2 months old is not effective in preventing the neurological
degeneration. We report here the carrier and prenatal diagnosis performed
in 6 families.
Methods: When the ATP7A mutation
in a family is known, genomic DNA was analyzed by PCR and direct sequencing
for the presence or absence of the mutant allele in 5 mothers, 1 maternal
aunt and 3 female fetuses. For the family mutation has not been found, the
copper concentration in cultured amniotic cells of a male fetus was
measured using an atomic absorption spectrometry.
Results: Three of the 5 mothers
are carriers; 2 are normal. A patient¡¯s maternal aunt is a carrier. DNA
analysis revealed that the fetuses in 3 families are females and are not
carriers. The 3 fetuses were born as normal individuals. One male fetus was
suspected as an affected child because his copper concentration in the
cultured fibroblasts confirmed that he is a patient with MND. He received
an early treatment and presented normal.
Conclusion: Molecular diagnosis of
carrier females and at-risk pregnancies is fast and reliable because random
inactivation of one of the X-chromosomes may cause normal clinical and
biochemical features in carrier. Measuring copper concentration in cultured
amniotic fluid cells is also a useful parameter for prenatal diagnosis.